Lower alkyl 4-substituted-2-(tertiary-aminoalkoxy) benzoates and their preparation



Patented June 16, 1953 l ration of Delaware v llhisainventionv relates to lower lkyl 4 -substituted -z-itertiary eaminoalkoxyl benzoates and to their-preparation; i a

, 1 lghe vcomll undsv of =our invention V have. the

.ger erahforrnula where'jjZ is; nitro amino, ,lower alkylamino 'or lowerjhydrqxyalkylaminojX is a lower alkylene radical; 'NRRi; is a tertiary-amino radical and IRz isa lower 'a1k3 l. radica1. These benzoates, especially the "compoundswhere'Z' is" N02, have utility as intermediates,for'instance, in "the preparation of .the corresponding quaternary saltswhich are "disclosed and claimed in' our- 00- pending application Serial""No. 245,248, filed September 5, 1951. In addition, some of these allryl 4 --'substituted-2 tertiary-aminoalkoxy) benzoates-" haveuseful pharmacologicalpropertiesi-snch as,--leca;l anesthetic activity-and analgesic-activitv.

inane-abovegeneral formula, the lower alkylene-radicardesignated as X-has preferably two to four carbom atoms and-hasits*two free valence bomflson" different carbon" atoms. Thus, X includes such' 'exarnples 'as and the like. Thetertiary-amino radical shown labove as NRR1 comprehends 1 dialkylamino radicals where -R and R1 arelower alk yl-groups, alike or different andeaoh alkyl group having one to .six carbon-atoms, such dialk'ylamino radicals including dimethylamino,u diethylamino; ethylmethylamino, 1 diisopropyl'amino, ethyl-n-propylamino, di neybutylamino, dim-.hexylamino, anduthe like. Further; !the:tertiaryamino :radicaldesignated as encompasses saturated :Neheteromonocyclicradicalszhavingsfive to six ring*atoms;.:illustratedc' bysl examples such .as lepiperidyl; (lower alkylated) elepiperidyl such asw2 -.methyl-L- piperidyl, iiaieethyl -l-piperidyl, 1 4 methyl-l-piperidyl, 256w dimethyl -la-piperidyl; 1.-+'pyrro1idyl; ('lower allkylated) t-1-pyrrolidyl s such -.as1 2-.methy1:-1- pmoli-d yl; r 2,5 dimethyl 1-1 A :pyrrolidyl 4-mor- LOWER ALKYLJ 4 SUBSTITUTED 2 TER- TIARY- AMINOALKOXY)BENZQATES AND THEIR PREPARATION Raymondn-0Q Clinton, North fireenbush tand Stanley 0. Laskowski, Menands, N. Y., assignors to, Sterling-Drug: Inc., NewYork', N; Y., ,a icorpo- NofDi-awing. Application September 5, 1951,

SerialrNo. 245,244

18 Claims. (Cl. 260+-'294.3)

pholinyl; and theilike. the above formula, when,.Z. stands forrlowerialkylamino, they lower' alkyl radical, designated-as R3 hereinbe1ow,-has preferably, onento six-..carbon..atoms,. including 'such' radicals as methyLethyl, n-propyl, n-butyl, isob rtyl, -n-amy1, zeamyl, n-hexyl, and the. like. When Z represents. lower hydroxyalkylamino, the lower hydroxyalkyl radical, designated as R3 hereinbelow, has preferably. two,-tosix carbon atoms, 1 including, radicals. such as 2-hydroxyethyl, -2-hydroxypropyl, 3-.hydrox-ypropyl, 3,-hydroxy-2emethylpropyl, 31-,hydroxy1-.2;,2rdimethylpropyl, 2=hydroxybuty1, 4-hydroxybutyl, 3,-hydroxyamyL..5hydroxyamyl, B-hydroxyhexyl, .and the like. i

.The-compoundsof our: invention vcanloe prepared. preferably according to the. procedure represented iby;,the following series. of equations where. X, NRRJ, R2 and R3 have the .meanings given hereinabove ,..and halogen is chlorine, bromine, ,iodineorrfluorine:

' OORz Thus, instep I; adowerxalkyl 4-nitro-2ehydroxy- 'benzoate (A) sis converted into, a lower alkyla 4- nitro-2-:(tertiaryeaminoalkoxvlbenzoate (C) by :reactioniz-withpa stertiary aminoalkyl:halide .(B)

:In step: II,- :the: l lower alkyl 4+nitro-2- (tertiaryaminoalkoxylbenzoate: (C): is reduced toiyield thew corresponding i lower 2 alkyl 4-amino-2- ter- -tiary-.aminoalkoxyl benzoate lD) which i is then alkylated to form the corresponding lower alkyl i-alkylaminowor 4 hydroxyalkylamino=2e(tertiary- -,i aminoalkoxylibenzoate 1 E9 'A specific illustration .of Lthis =series of reactions 'isthe :for-

mati'on of ethyl l -n-butylamino-Z-iz-diethylaminoethoxyolbenzoate by first reacting ethyh 4- nitro-zehydroxybenzoate; preferablyinf the -:form

11 12 Additional lower alkyl 4-amino-2- (tertiarY- of their monohydrochlorides, are ethyl 4-n-pro-, aminoa1koxy benzoates which can be prepared py1amino-2 (2 diethylaminoethoxy) benzoate, according to the foregoing procedures include ethyl 4-n-amy1amino-2-(Z-diethylaminoethoxy) the following: ethyl 4-amino-2-(2-d1'm pevsosrpwvqepp 11-11-11 mm; m I I 110101 1115 0 11 1211141115 11016911111 ya 11 9 ,1/1 *1-1111 111/1 -1-11 WW 1 r4 1 1111111111111111m111101111 11111111 111111 111111111 1111111111111 1 15" 1111/11/11111/1111/1111/11111 11 11 111 111 1 1 1 9 1111 1-1111110-5- 1a11,1111- 01 111111 1110110p1q10011 011g11 111 11111] 1-11-1111 hydrochloride.

Analyses o 'n NRR. R, 5; Formula N 01 Oalod. Found Calod Found 2 NC7H14 OHzOHs 153:0-154. 0 CIHHZoNflOE- H01 7. 24 7. 9. 16 9. 14 2 NCiHaO CH2CHB 207. (F208. 0 ClbHiBNflOt. H01 7. 77 7. 81 9. 83 9. 92 3 NC4HaO CHBOH: 1 12. 0-144. 6 CitHnNiOu. H01 7. 48 7.79 9. 46 9. 25 2 NCsHio OHzCHa 191. 0-191. 5 CmHzzNnOs. H01 7. 81 7. 82 9. 88 9. 90 2 O4H80 CH3 6. 0-206- 4 CuHiaNnOu. H01 0 4. 04 l 4. 05 10. 22 10. 21' 2 N CeHn 20113 180. 8-182. 6 CITHHNZOB. H01 7. 52 7. 22 9. 51 9.38 3 NCaHm CHzCHz 158. 2-159. 6 CisHioNiOt. H01 7. 24 7. 03 9. 16 8. 92 3 N(O2H6)Z CH2CH3 164. 8 165. 6 CmHiiNzOt. H01 7. 77 7. 87 9. 83 9. 72 2 N(O;H5)z CHzOHiCHz 153. 4-155. 4 CloHnNrOa. H01 7. 77 7. 95 9. 83 9. 83 2 N(C2Ht)2 CH3 156. 9159. 2 CuHzoNiOs. H01 8. 42 8. 38 10. 65 10. 50

e Nitro nitrogen as determined by titration with standard titanous chloride in glacial acetic acid solution.

Additional lower alkyl 4-nitro-2- (terti-ary- 20 this solution was added a small amount of ethyl aminoalkoxy) benzoates which can be prepared according to the foregoing procedures include the following: ethyl 4-nitro-2-(2-dimethylamino-1- propoxy)benzoate; isobutyl nitro-2-[3-(l-pyrrolidyl) propoxy] benzoate; ethyl 4-nitro-2 2- '(2,5 dimethyl 1 pyrolidyl)ethoxylbenzoate;

methyl 4 nitro 2 (4 dimethylaminobutoxy) benzoate; n-propyl 4-nitro 2 [2-(di-n-buty1- amino)ethoxylbenzoate; n-butyl 4-nitro-2-[3- (a methyl 1 piperidyl) propoxylbenzoate; nhexyl 4-nitro-2-[2- (3-ethyl-1-piperidyl) ethoxy] benzoate; n-amyl 4-nitro-2-[3- (2-methyl-1-pyrrolidyl) propoxylbenzoate; and the like.

(2). Lower allcyl 4-amino-2-(tert Wy-ominoallcowy) benzoates ly, over a period of about ten minutes, 35.? g. of I ethyl 4-nitro-2- (2-diethylaminoethoxy) benzoate The resulting mixture was heated with stirring for another thirty minutes, after which time an excess of solid sodium bicarbonate (about 15 g.) was cautiously added. The mixture was stirred for an additional ten minutes and then filtered through a filter'aid which was subsequently washed with hot ethanol. The combined filtrate and washings were concentrated by distilling in vacuo, thereby yielding an oily residue which was taken up with ethyl acetate. The ethyl acetate was dried over anhydrous calcium sulfate and taken to dryness in vacuo, yielding, as a pale orange, slightly viscous oil, 27.4 g. of the product, ethyl 4-amino-2-(z diethylaminoethoxy) benzoate.

The preparation of ethyl 4-amino-2-(2-diethylaminoethoxy) benzoate in the form of its monohydrochloride salt was accomplished as follows: To a solution of 12.0 g. of ethyl 4-amino-2-(2- diethylaminoethoxy)benzoate dissolved in 50 ml. of absolute ethanol was added 8.50 ml. of an ethanolic solution of hydrogen chloride (0.1843 g./,m1.; enough HCl to produce the monohydrochloride). The solution was mixed well, taken to dryness in vacuo, ethyl acetate added and removed in vacuo, and the remaining residue dissolved in a small amount of isopropanol. T0

The dihydrochloride salt of the above 4-amino:

benzoate was prepared by dissolving it in ethyl acetate and treating the solution with an excess of ethereal-hydrogen chloride. The mobile colorless oil which separated crystallized readily when triturated. The solid was filtered, washed well with ethyl acetate and recrystallized twice from absolute ethanol-ethyl acetate. There was thus obtained ethyl 4-amino-2-(2-diethylaminoethoxy)benzoate dihydrochloride, M. P. 173.6- 173.9 C. (cor.) [dried three days at 50 C.].

Anal.---Calcd. for C15H24N20s-2HC1: C, 50.99; 11% 7.42; 01, 20.07. Found: C, 51.14; H, 7.36; Cl,

Ethyl 4- amino -2- (2-diethylaminoethoxy) benzoate was converted into its phosphoric acid addition salts as follows: A solution of the ester in absolute ethanol was treated with a molar equivalent of phosphoric acid in absoluteeth- The precipitated crystalline phosphate was collected and recrystallized four times from ethanol, yielding ethyl 4-amino- 2 (2 diethylaminoethoxy) benzoate phosphate,

M. P. 168.7169.6 C. (cor.).

AmL-Calcd. for C15H21N2O7P: HaPO4, 25.91;

N 7.40. Found; HsPOi, 25.30; N 7.41.

n-Butyl 4-amino 2-(2 diethylaminoethoxy) benzoate was prepared as follows: A stirred mixture 01 71.5 g. of powdered iron, 300 ml. of

ethanol, 75 ml. of water and 1 ml. of concentrated hydrochloric acid was brought to a boil. Heat was removed and 80.0 g. of n-butyl 4-nitro-2- (2 diethylaminoethoxy) benzoate hydrochloride was added portion-wise at such a rate as to maintain gentle boiling. After addition of the nitro compound had been completed, the reaction mixf ture was refluxed with stirring for thirty minutes. (about 20 g.) was cautiously added and reflux- ;ing and stirring were continued for an additional;

Then an excess of sodium bicarbonate zicsziesz eneminiites- :Ihe reactionmixt-ure-was.;fi e hotcandltheifiltrate l .as-iconcentrated in vacu to r lcmove all :the ethanol. {Hie-product, which en mted as: a- .d-1' s.tinct slayer; wasv extracted with ethyl acetate. The ethyl acetate 'solution was dried oyerw anhydrous calcium sulfate and l concentrated-l in lVfl'GLlOi to yield, as 2 a straw :colored oil, :n-.butyl- .4-amino-2- (Z-dithylaminoethoxy) henzoate. llhis ester was wconverted .into =its phosphoric-acid addition salt as ,ifollows ,To a hot 1 solution of .46 rg.

die hylaminoethoxyl henzoateadissolvedin a: minimum quantit L addedeanhot ethanolicnsolution of 1-7 -.-2 .-g. of85% phosph ri acid. n whit s lid r ed wsenarat d from:.the @hot; solution, whichcwas diluted with ethyl acetate; coolemand-filtered. iI'heesolid was recrystallized-several t mesi-iromi absolute thano ontaining .a-lsmall lquantity of watch thereby yielding, as rosettes of white ;need1es,=.n-h11ty -:511111110 ;-.2-- (2 diethylaminoethoxy) benzoate phosphate, M.--,P. 1154;5-1-555" 1 C. (con).

w Ethylwl +amino .2- [*3 61 pip d l) D TQD XTY F henzoateywas :prepared.laccordinggto the procedin-c adescrihed above l for @the preparation. :of n=c=buty1-.4 -.;amino -:2 -42 -.-.diethylaminoethoxy) .benZoa-t-m but: using 567.23g. .of .powderedqiron; 400 m1. lof ethanol, 1110011111. of .;water, .1 ml. of concentrated hydrochloric :acid, 76 g. :of ethyl 1 4- nitro -I:2-- ';E3 all -ypiperidyllpropoxylbenzoate hydrochloride andabout60 acct sodium bicarbonate. cxtractv ieldedear solid 1 product. .{I-This;so1id-when recrystallized from rethanol --.yielded, r as white needles, li -ethyl -4' amino -12 1E3 (.1 -;:piperiidyl) vpropoxylbenzoatc, ;M.': P. .1-09:2-,110 .1 10. (con). w-AnaL- Galcd; .afor ENE-126N203 oNn, --9.14. ND, 8290." I Ethyl -14 -zi.amino- -:.:2--- :[3 l- 1,1 -;zpiperidy1 propoxyll-benzoateuphosphatemprepared ass-above, meltcdaat116Q52+16l569 cor.) whenlrrecrystallizec'l several times from absolute ethanol.

emcle-eflalcdr foruCmHzsNzOuHzPOr: ND, (6493;

Vacuum :eyaporationpf the; ethyl ,acetate ben-zoate; .wasrobtained as an oil. 'This ester was converted intoits diphosphate as follows: A solutionof; 9.; ;-.'g.-:of methyl hair ine-.2 [2- (4emorpholinyl)-ethoxylbenzoate-inh25 'ml. oim-etha-nol was teated -withea solution of 319g. .of. phosphoricacid in 251ml. cof: methanol, whereupon there r separated immediately. a gummy material. Et yl acetateswas.addedflto the :mixture and the prec pitated material wasatrit uratedwhile warming. The supernatant-liquid was decanted ,and hei eut my 'imaterialwas triturated, several times Withr warmgabsoluteethanol, vwhereupon l-solidification i-finally resulted. The solid was filtered and recrystallized l y ,snspending it in hot .absolute ethanol and adding hot water dropwise until: the solution-became; clear, treating: the solutioncwwith :Jdecolerizing gcharcoal, filtering and allowing the filtrate to cool. The finely divided white salt that separated was collected and dried in v-acuo at ;"-*C.,'=yielding 5.5-g. of methyl jlarnino --2 [-2 -*(4 -;morphol-inyl)ethoxyl -be1izoate diphosphatepM. P: l51'.3-152.1 C. (con) Analr-Galcd for C14H2bN2O4 -2I-I3POi: Np, 5:88; 2H3PO4,=41*.16. Found: N 596; 2H3PO4,-40;85.

The foregoing reductions of the lower alkyl 4 nitro 2 (tertiarya-minoalkoxylbenzoates evaporatedto drynessl The resulting resid-ue is dissolved inabsol-uteethanol and is treated with asolution of 85% phosphoric acid in absoute ethanol-to yield the corresponding lower alkyl *22 r(tertiaryaminoalkoxylbenzoate phosphate.

' z-*Additional loweralkyl 4-amino-2-(tertiary above procedures are-given -in Table II.

i NOQHEO =4-morpholiny1 The-crystalline basemelt'ed at 98.0-99.83'0. (cor,).3 .0alcd; :for iCisHi'zN 20;: N n; 9.52 f l .The crystalline basemelted at 106.8108.0$,G,-..(cor.)

Additional lower alkyl 4-amino-2-(tertiaryaminoalkoxy)benzoates which can be prepared according to the foregoing procedures include the following: ethyl l-amino-2-(2-dimethylamino-1-propoxy)benzoate; isobutyl 4-amino-2-[3- (l-pyrrolidyl) propoxylbenzoate; ethyl 4-amino- 2- [2- (2,5 dimethyl-l-pyrrolidyl) ethoxylbenzoate; methyl 4-amino-2 -(4-dimethylaminobutoxy)benzoate; n-propyl 4-amino-2-[2-(di-nbutylamino) ethoxylbenzoate; n-butyl l-amino- 2- [3- i-methyl l-piperidyl) propoxylbenzoate; n-hexyl 4-amino-2- [2- (3-ethyl-1-piperidyl) ethoxylbenzoate; n-amyl 4-amino-2-[3-(2-methyll-pyrrolidyl)propoxylbenzoate; and the like.

(3). Lower aZkyZ 4-allcylaminoalkyamino Z-(tertiary aminoalkowmbenzoates 'diethylaminoethoxy)benzoate, 24.1 g. of zinc dust, 22.6 g. of glacial acetic acid and 450 ml. of dry benzene was added 8.0 g. of n-butanal (nbutyraldehyde) dissolved in 50 ml. of dry benzene over a fifteen minute period. After the mixture had been stirred for one hour,an additional 1' ml. of n-butanalwas added and stirring The zinc acetate was filtered off and washed with hot dilute acetic acid'and benzene. vThe cooled filtrate was made basic to litmus with concentrated ammonium hydroxide, the benzene layer was separated and the aqueous solution was extracted three times with benzene. After the combined benzene layerand extracts had been dried over anhydrous calcium sulfate, the ben zene was removed by distilling in vacuo, yielding, as a straw colored oil, ethyl 4-n-butylamino- 2-(Z-diethylaminoethoxy)benzoate. This ester was converted into its monohydrochloride salt as follows: Eleven grams of the ester was dissolved in ethyl acetate and was treated with an excess of 20% by weight of ethanolic hydrogen chloride, whereupon a gummy material separated immediately. The supernatant liquid was decanted from the gum and the latter was triturated twice with warm ethyl acetate. The

gummy material was then dissolved in a minimum amount of hot ethanol, 12 g. of ethyl 4-hbutylamino 2 -(2-diethylaminoethoxy) benzoate was added and the solution was cooled. Absolute ether was then added to turbidity, whereupon a cream colored crystalline precipitate separated. The mixture was diluted to about 500 ml. with absolute ether. The precipitate was collected and recrystallized once from absolute ethanol-absolute ether with decolorization, using decolorizing charcoal, and a second time, with decolorization, from ethanol-ethyl acetate. There was thus obtained ethyl 4-n-butylamino-2-(2-diethylaminoethoxy benzoate hydrochloride, M. P. 160.5- 161.8 C. (cor.).

AnaZ.Calcd. for C19H32N2O3 HCI: 9.50. Found: N 7.36; Cl, 9.45.

When the above procedure is followed but using n-propanol, n-pentanal and n-hexanal, in place of n-butanal, the resulting products, in the form ND, 7.51; oi,

4-n-butylamino-2-(Z-diethylaminoethand -hydrorycontinued for an additional fifteen minutes;

of their monohydrochlorides, are ethyl -n-propylamino-2 (2 diethylaminoethoxy)benzoate, ethyl 4-n-amylamino-2-(Z-diethylaminoethoxy) benzoate and ethyl 4-n-hexylamino -2-(2-diethyle aminoethoxy)benzoate, respectively.

When the above procedure is followed'but using, in place of ethyl 4-amino-2-(2-diethy1aminoethoxy) benzoate, methyl 4-amino-2- [3- (l-piperidyl) -propoxy]benzoate, (2,6-dimethyl-1 piperidyl) ethoxy-lbenzoate, nbutyl 4-amino-2-[2-2 methyl-l-piperidyl) ethoxylbenzoate or ethyl 4-amino-2E2-(4-morpholinyl)ethoxy]benzoate, there is obtained, in the form of their monohydrochlorides, methyl 4-n butylamino-2-[3 -(1 piperidyl) propoxylbenzoate, n-propy 4-n-butyl-amino-2-[2-(2,6-dimethyl-l-piperidyl) ethoxylbenzoate, n-butyl 4n-bu'- tylamino-Z-[2-(2-methyl-1 piperidybethoxylbenzoate or ethyl 4-n-butylamino-2el2-(4-iriorpholinyl) ethoxy] benzoate, respectively.

Ethyl 4- (5-hydroxyamylamino) -2- (2-diethylaminoethoxy benzoate was obtained, as an oil, following the above procedure but using 26.0 g. of ethyl 4-amino benzoate, 11.3 g. of 5-hydroxypentanal, 24.1 g. of zinc dust, 22.6 g. of glacial acetic acid; and 5 00 ml. of dry benzene. "Ethyl 4-(5-hydroxyamylamino) -2- (Z-diethylaminoethoxy) benzoate monohydrochloride, M. P. 132.2-133.4 C. (cor.) was obtained following the procedure disclosed above for preparing ethyl 4-n-butylamino-2-(2-diethylaminoethoxy) benzoate monohydrochloride.

Anal.Calcd. for C20H34N204'HC11 N 6.95; Cl, 8.79.- Found: N 7.07; Cl, 9.05. When the above procedure was followed but using, in place of ethyl 4-amin0-2-(2-diethylaminoethoxy)benz0ate, n-propyl 4-amino-2-(2-diethylarninoethoxy) benzoate and ethyl 4-amin0- 2-[2-(2,6-dimethyl 1 piperidyl) ethoxylbenzoate, there was obtained, as oils, n-propyl 4-(5- hydroxyamylamino) -2 -(2-diethylaminoethoxy) benzoate and ethyl 4-(5-hydroxyamylamino) 2- [2-(2,6-dimethyl l-piperidyl)ethoxylbenzoate, respectively.

When the above procedure is followed but using, in place of 5-hydroxypentanal, 3-hydroxypropanal, 4-hydroxybutanal, 3-hydroxybutanal benzene, with decolorization using decolorizing charcoal, yielding ethyl 4(3-hydroxy-2,2dimethylpropylamino) 2 [2 (2,6 dimethyl 1 'piperidyl)ethoxylbenzoate, M. P. 90.0-91.0 C.

(cor.) [dried in vacuo at 65 0.]

Analcaled. for C23H3sN2O4I C, 67.94; H, 9.42; N 6.89. Found: C, 68.06; H, 9.31; N 6.81.

Alternatively, the foregoing reductive alkylations can be carried out using, in place of zinc dust and glacial acetic acid, hydrogen under 2-(2 diethylaminoethoxy)- 2:213 oPressureu'rim-flthev; presence :oma hydrogenation .vratalystzssuchLassplatinum.l

Qtbenlowenalkyrliaalkylaminoegor 4-hydroxy- -alkylaminom (tertiaryeaminoalkoxyrbenzoates 4-amino compounds. This mode of alkylatiorris illustrated -byl. hcating ethyl- 4=amino-2' (2;-di- "ethflaminoethoxy)fbenzoate. ;with methyl; iodide, ethyl bromide,"z hydroxyethyl,bromidam propyl iodide, n-butyl bromide or 5-hydroxypent'yl chloride in the presence of a hydrogen halide acceptor such as potassium carbonate to yield, respectively, ethyl 4-methylamino-2"-(2-diethylaminoethoxy)benzoate, ethyl 4rethylamino-2-(2-diethylaminoethoxyhbenzoatel ethyl 4-(2-hydroxY- ethylamino) -2-(2-diethy1aminoethoxy) benzoate, ethyl 4-n-propylamino-.2;-l(2 diethylaminoethoxy) benzoate, ethyl 4-n-buty1amino-2-(2-diethy1- -aminoethoxyd benzoate rand "ethyl 4-:(5-hydroxyamylam-ino) -2 t z diethylaminoethoxy) benzo ate.

we claimt l-i' A- compou-rid'having the for-mula where Z is a member of the group consistingof *nitro, aminq lower alkylamino -and lower =hydroxyalkylamino, X is a--l-ower alkylene -radica1 whose -two free valencewonds are on different carbon atomsyNRRi is-a member of the group consisting of lower dialkylamino, l-piperidyl, (lower alkylated) 1 -="piperidyl 1 pyrr'olidyl,

v (lower alkylated).e1epyrrolidyltauch4ermorpholinyl, ands-R2 is a lower alkyl radical.

M2. Alcompound having the-formula OXN (lower alkyl);

where X is a lower alkylene radical whose two free valence bonds are on different carbon atoms and R2 is a lower alkyl radical.

whicho can-be=:preparedsaccording toutheaabcve I ;pyrro1idy1 1121 012033 pared ,by; direct alkylationjbf therorrfiwcnding 455 having the formula 2&642 432 where X is a lower alkylene radical whose two free valence bonds-are onfid-iiferent carbon atoms and R2 is a lower alkyl radical. V

4. A compound having thefcrmula "where X is a -lower alkylene radica1- WhOSe two free valence bonds are on different carbon atoms, NRRr-is -a, l piperidyl radical and =-Rz is a lower -alkyl radical.

5. A compound having the formula .wherefJX is; a lloweriialk ylene radical whose; two free-valence,bondsare on different carbonaI-oms, ,NRRiiis a floweralkylated)-l;piperidyl radical LandJRgisa lower alkyl radical. v a

":6. A compound having the formula ing,

50 where X is a lower alkylene radical whose two free valence bonds are ondi'fferent carbon atoms, PNRRl'iSXfl Zsmethyhl piperidyltradical and Rz-is la lowertalkyleradical. V

{MA process fon-thelpreparationpf a compound o er-Nam 455 where X is a lower alkylene radical whose two free valance bonds are on different carbon atoms, lNRRl is a member of the group consisting of lower dialkylamino, l-piperidyl, (lower alkylated)- l-piperidyl, l-pyrrolidyl, (lower alkylated)-lpyrrolidyl and 4-morpho1inyl, and R2 is a lower alkyl radical, which comprises treating a member of the group consisting of a lower alkyl 4-nitro-2-hydroxybenzoate and a metal salt thereof with a tertiary-aminoalkyl halide of the formula, halogen-X-NRR1, and

J 15 treating the resulting lower alkyl 4-nitro-2- (tertiary-aminoalkoxy)benzoate with a reducing agent effective to reduce nitro groups to amino groups.

8. A process for the preparation of a compound having the formula (IJOORZ where X is a lower alkylene radical whose two free valence bonds are on different carbon atoms, NRR1 is a member of the group consisting of lower dialkylamino, l-piperidyl, (lower -alkylated)- l-piperidyl, l-pyrrolidyl, (lower a1kylated)-1- pyrrolidyl and4-morpholinyl, which comprises treating the corresponding lower alkyl 4-nitro-2- (tertiary-aminoalkoxy)benzoate with a reducing agent effective to reduce nitro groups to amino groups.

9. A processfor the preparation of a lower alkyl 4 amino-2-(dialkylaminoalkoxy)benzoate having the formula NHz XN (lower alkyl):

where X is a lower'alkylene radical whose two free valance bonds are on different carbon atoms and R2 is a lower alkyl radical, which comprises treating the corresponding lower alkyl-4-nitro-2- (dialkylaminoalkoxy)benzoate with a reducing agent effective to reduce nitro groups to amino groups.

10. A process for the preparation of a lower alkyl 4 amino-2-(diethylaminoalkoxy)benzoate having the formula 000R: where X is a lower alkylene radical whose two free valence bonds are on different carbon atoms and R2 is a lower alkyl radical, which comprises treating the corresponding lower alkyl 4-nitro- 2-(diethylaminoalkoxy)benzoate with a reducing agent effective to reduce nitro groups to amino groups. I

11. A process for the preparation of a lower alkyl 4 amino 2-(tertiary-aminoalkoxy)benzoate having the formula where X is a lower alkylene radical'whose two.

free valence bonds are on different carbon atoms, NRR1 is a l-piperidyl radical and R2 is alower alkyl radical, which comprises treating the corresponding lower alkyl 4-nitro-2-(tertiaryaminoalkoxy)benzoate with a reducing agent effective toreduce nitro grn'zip to amino groups.

12. A process for the preparatioi'r'of 'a3-lower alkyl 4 amino 2 (tertiary-arrfinoalkoxy)beh= zoate having the formula Where X is alower alkylene radical whose' two free valence bonds are on different carbon atoms, NRRr is a (lower alkylated)-1-piperidyl radical and R2 is a lower alkyl radical, which comprises treating the corresponding lower alky14-nitro-2- (tertiary-aminoalkoxy)benzoate with a reducing agent effective to reduce nitro groups to amino ro p 13..'A process. for the preparation of a lower alkyl 4-amino-2- (tertiary aminoalkoxy) benzoate having the formula I I v 000 111 where X is a lower alkylene radicalwhosetwo free valence bonds are on different carbon atoms, NRR1 is a 2-methyl-l-piperidyl radical and R2 is a lower alkyl radical, which comprises treating the corresponding lower alkyl 4-nitro-2- (tertiaryaminoalkoxy benzoate with a reducing agent References Cited in the file of .this patent UNITED STATES PATENTS Name I Date Blicke May 29, 1945 OTHER REFERENCES Moore, Journal of American Pharmaceutical Association, July 1944, pp. 193-204.

Number 

1. A COMPOUND HAVING THE FORMULA 